1. Field of the Invention
The present invention relates generally to the fields of molecular medicine, drug and gene delivery, imaging, and, more specifically, to novel compositions and methods for treating and/or diagnosing diseases such as cardiovascular diseases and brain diseases.
2. Description of the Related Art
The vascular endothelium has been recognized as an important target for therapeutic interventions which use liposomes or other particles to carry drugs and/or genes. See Ding et al., Molecular Interventions 2006; 6(2):98-112.; Hajitou et al., Trends in Cardiovascular Medicine 2006; 16(3):80-88. Specific adhesion to normal or pathological organs has been reported using ligands tailored to vascular zip codes or luminally-expressed pathological targets. See Ruoslahti, Biochem Soc Trans 2004; 32:397-402.; Zhang et al., Circulation 2005; 112(11):1601-1611.; Brissette et al., Curr Opin Drug Discov Dev 2006; 9(3):363-369. Other previous studies have targeted particles to tumor vessels and tumor cells, effectively combining the enhanced permeability and retention effect within tumors with the effect of the targeting ligand. See Ding et al., Molecular Interventions 2006; 6(2):98-112.; Torchilin, Nature Reviews Drug Discovery 2005; 4(2):145-160.
Among various drug-gene delivery particles, targeted phospholipid-based liposomes have been widely studied but have had limited clinical impact. In limited pre-clinical studies, antibody targeting of liposomes to intravascular targets has shown impressive localization of delivery vehicles and subsequent therapeutic effect. See Raffaghello et al., Cancer Lett 2003; 197(1-2):151-155.; Lukyanov et al., Journal of Controlled Release 2004; 100(1):135-144. However, a major drawback of antibody targeted liposomes is low tissue penetration and high molecular weight. In contrast, small peptides and small molecules that selectively recognize cell surface markers can be employed to target vehicles. See Torchilin, Nature Reviews Drug Discovery 2005; 4(2):145-160.; Shadidi et al., Drug Resistance Updates 2003; 6(6):363-371.; Schiffelers et al., Journal of Controlled Release 2003; 91(1-2):115-122.; Lestini et al., Journal of Controlled Release 2002; 78(1-3):235-247.
The short linear peptide CRPPR (SEQ ID NO: 1) has previously been reported to specifically bind to the heart endothelium. See Zhang et al., Circulation 2005; 112(11):1601-1611. Other short linear arginine-containing peptides were similarly identified by phage display and demonstrated substantial but less specific cardiac targeting. See Zhang et al., Circulation 2005; 112(11):1601-1611. However, it is unclear whether any of these peptides can be used for targeting drug-gene delivery particles to the vasculature or what features may be required to maximize delivery.
Thus a need exists for a composition that can be used to specifically deliver compounds to a cell of interest while also maximizing efficacy, decreasing art known immunogenic effects against the composition, and expanding the potential applications of the composition to other diseases and utilities. The present invention provides for these and other advantages, as described below.